crossing96/oncoscreening huggingface dataset:
Risk of several cancers is higher in urban areas after adjusting for socioeconomic status. Results from a two-country population-based study of 18 common cancers.	Some studies suggest that there are urban-rural variations in cancer incidence but whether these simply reflect urban-rural socioeconomic variation is unclear. We investigated whether there were urban-rural variations in the incidence of 18 cancers, after adjusting for socioeconomic status. Cancers diagnosed between 1995 and 2007 were extracted from the population-based National Cancer Registry Ireland and Northern Ireland Cancer Registry and categorised by urban-rural status, based on population density of area of residence at diagnosis (rural <1 person per hectare, intermediate 1-15 people per hectare, urban >15 people per hectare). Relative risks (RR) were calculated by negative binomial regression, adjusting for age, country and three area-based markers of socioeconomic status. Risks were significantly higher in both sexes in urban than rural residents with head and neck (males RR urban vs. rural = 1.53, 95 % CI 1.42-1.64; females RR = 1.29, 95 % CI 1.15-1.45), esophageal (males 1.21, 1.11-1.31; females 1.21, 1.08-1.35), stomach (males 1.36, 1.27-1.46; females 1.19, 1.08-1.30), colorectal (males 1.14, 1.09-1.18; females 1.04, 1.00-1.09), lung (males 1.54, 1.47-1.61; females 1.74, 1.65-1.84), non-melanoma skin (males 1.13, 1.10-1.17; females 1.23, 1.19-1.27) and bladder (males 1.30, 1.21-1.39; females 1.31, 1.17-1.46) cancers. Risks of breast, cervical, kidney and brain cancer were significantly higher in females in urban areas. Prostate cancer risk was higher in rural areas (0.94, 0.90-0.97). Other cancers showed no significant urban-rural differences. After adjusting for socioeconomic variation, urban-rural differences were evident for 12 of 18 cancers. Variations in healthcare utilization and known risk factors likely explain some of the observed associations. Explanations for others are unclear and, in the interests of equity, warrant further investigation.	bladder
Importance of the neutrophil-to-lymphocyte ratio in muscle-invasive and non-muscle invasive bladder tumors.	INTRODUCTION: To research the importance of the neutrophil-to-lymphocyte ratio (NLR) in muscle-invasive bladder cancers (MIBC) and non-muscle invasive bladder cancer (NMIBC). METHODS: Data of 198 patients who underwent TUR-TM in our clinic were retrospectively evaluated. Patients were divided into two groups: group-I (MIBC) and group-II (NMIBC). The neutrophil and lymphocyte counts, NLR, hemoglobin and hematocrit values, tumor numbers, sizes and degrees of patients were recorded. Within the inter-group comparison, Mann-Whitney U test was used for the values stated with measuring, whereas a Chi-square test was used for the values stated with counting. The cut-off value for the NLR was determined with ROC curve. RESULTS: The NLR values of group-I and group-II were found as 4.14 ± 2.76 and 3.36 ± 2.88, respectively (p = 0.03). Whether the NLR carries a differential property was evaluated with ROC curve. The cut-off value was estimated as 3.96 according to the Youden index. With this value, sensitivity was found as 50%, specificity was 22.8% and AUC was 0.615 (p = 0.03). DISCUSSION: According to the data in this study, it can be said that Ta-T1 tumors are likely to be invasive by 50% if the NLR value is greater than 3.96.	bladder
Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer.	"Using complete genome analysis, we sequenced five bladder tumors accrued from patients with muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) and identified a spectrum of genomic aberrations. In three tumors, complex genotype changes were noted. All three had tumor protein p53 mutations and a relatively large number of single-nucleotide variants (SNVs; average of 11.2 per megabase), structural variants (SVs; average of 46), or both. This group was best characterized by chromothripsis and the presence of subclonal populations of neoplastic cells or intratumoral mutational heterogeneity. Here, we provide evidence that the process of chromothripsis in TCC-UB is mediated by nonhomologous end-joining using kilobase, rather than megabase, fragments of DNA, which we refer to as ""stitchers,"" to repair this process. We postulate that a potential unifying theme among tumors with the more complex genotype group is a defective replication-licensing complex. A second group (two bladder tumors) had no chromothripsis, and a simpler genotype, WT tumor protein p53, had relatively few SNVs (average of 5.9 per megabase) and only a single SV. There was no evidence of a subclonal population of neoplastic cells. In this group, we used a preclinical model of bladder carcinoma cell lines to study a unique SV (translocation and amplification) of the gene glutamate receptor ionotropic N-methyl D-aspertate as a potential new therapeutic target in bladder cancer."	bladder
Co-expression of HER3 and MUC1 is associated with a favourable prognosis in patients with bladder cancer.	OBJECTIVES: To investigate the functional impact of the interaction of MUC1 with the epidermal growth factor receptors HER3 and HER4 in patients with bladder cancer. PATIENTS AND METHODS: Using reverse transcription quantitative polymerase chain reaction, we examined MUC1 expression in 82 bladder cancer biopsies previously examined for the expression of HER3. RESULTS: Patients expressing high MUC1 had a favourable survival when the expression of HER3 was also high compared with when the expression of HER3 was low (P = 0.004). When MUC1 expression was low, HER3 co-expression did not influence the prognostic value of MUC1 (P = 0.488). MUC1 expression had no correlation with survival, tumour stage or grade, or to the prognostic value of HER4. CONCLUSIONS: A high MUC1 expression was associated with a favourable prognosis in patients with bladder cancer when the expression of HER3 was also high. This suggests an involvement of HER3 in MUC1 function in bladder cancer.	bladder
Genetic instability persists in non-neoplastic urothelial cells from patients with a history of urothelial cell carcinoma.	Bladder cancer is one of the most common genitourinary neoplasms in industrialized countries. Multifocality and high recurrence rates are prominent clinical features of this disease and contribute to its high morbidity. Therefore, more sensitive and less invasive techniques could help identify individuals with asymptomatic disease. In this context, we used the micronucleus assay to evaluate whether cytogenetic alterations could be used as biomarkers for monitoring patients with a history of urothelial cell carcinoma (UCC). We determined the frequency of micronucleated urothelial cells (MNC) in exfoliated bladder cells from 105 patients with (n = 52) or without (n = 53) a history of UCC, all of whom tested negative for neoplasia by cytopathological and histopathological analyses. MNC frequencies were increased in patients with a history of UCC (non-smoker and smoker/ex-smoker patients vs non-smoker and smoker/ex-smoker controls; p<0.001), in non-smoker UCC patients (vs non-smoker controls; p<0.01), and in smoker/ex-smoker controls (vs non-smoker controls; p<0.001). Patients with a history of recurrent disease also demonstrated a higher MNC frequency compared to patients with non-recurrent neoplasia. However, logistic regression using smoking habits, age and gender as confounding factors did not confirm MNC frequency as a marker for UCC recurrence. Fluorescent in situ hybridization analysis (using a pan-centromeric probe) showed that micronuclei (MN) arose mainly from clastogenic events regardless of UCC and/or smoking histories. In conclusion, our results confirm previous indications that subjects with a history of UCC harbor genetically unstable cells in the bladder urothelium. Furthermore, these results support using the micronucleus assay as an important tool for monitoring patients with a history of UCC and tumor recurrence.	bladder
PAI-1 leads to G1-phase cell-cycle progression through cyclin D3/cdk4/6 upregulation.	The canonical function of plasminogen activator inhibitor-1 (PAI-1/SERPINE1) is as an inhibitor of urokinase-type plasminogen activator for blood clot maintenance, but it is now also considered a pleiotropic factor that can exert diverse cellular and tumorigenic effects. However, the mechanism controlling its pleiotropic effects is far from being understood. To elucidate the tumorigenic role of PAI-1, we tested the effects of PAI-1 after manipulation of its expression or through the use of a small-molecule inhibitor, tiplaxtinin. Downregulation of PAI-1 significantly reduced cellular proliferation through an inability to progress from the G(0-G1) phase of the cell cycle. Accordingly, overexpression of PAI-1 augmented proliferation by encouraging S-phase entry. Biochemically, cell-cycle arrest was associated with the depletion of the G(1)-phase transition complexes, cyclin D3/cdk4/6 and cyclin E/cdk2, in parallel with the upregulation of the cell-cycle inhibitors p53, p21Cip1/Waf1, and p27Kip1. PAI-1 depletion significantly decreased the tumor size of urothelial T24 and UM-UC-14 xenografts, and overexpression of PAI-1 substantially increased the tumor size of HeLa xenografts. Finally, immunohistochemical analysis of human bladder and cervical tumor tissue microarrays revealed increased expression of PAI-1 in cancerous tissue, specifically in aggressive tumors, supporting the relevance of this molecule in human tumor biology. IMPLICATIONS: Targeting PAI-1 has beneficial antitumoral effects and should be further investigated clinically.	bladder
Photodynamic therapy with the novel photosensitizer chlorophyllin f induces apoptosis and autophagy in human bladder cancer cells.	BACKGROUND AND OBJECTIVES: Our group recently synthesized a new, low-cost photosensitizer, chlorophyllin f. In this study, the effects of chlorophyllin f-mediated photodynamic therapy (PDT) and its potential mechanisms were examined in human bladder cancer cells. MATERIALS AND METHODS: MitoTracker® Green probe and LysoTracker® Green probe were used to label mitochondria and lysosomes, revealing the intracellular localization of chlorophyllin f in 5637 and T24 cells by confocal laser scanning microscopy (CLSM). The cells were treated with chlorophyllin f-mediated PDT; the photo-cytotoxicity of chlorophyllin f was monitored using the Cell Counting Kit-8 assay, and apoptosis was measured by Annexin V-FITC/PI dual staining. Western blotting, transmission electron microscopy (TEM), and staining with Cyto-ID® Autophagy Detection dye, monodansylcadaverine (MDC) and acridine orange were performed to assess autophagy. The role of autophagy was examined by measuring cell viability and apoptosis in both cell lines pretreated with the autophagy inhibitor 3-methyladenine (3-MA). RESULTS: Chlorophyllin f showed affinity for mitochondria and lysosomes. It exhibited significant photocytotoxicity, resulting in a maximum of 86.51% and 84.88% cell death in 5637 and T24 cells, respectively. Additionally, chlorophyllin f-mediated PDT (f-PDT) also induced a significantly higher percentage of apoptosis in treated cells compared to the control groups (P < 0.05). Moreover, the expression of Beclin1 protein and the proportion of LC3-II:LC3-I in both cell lines significantly increased after f-PDT. Autophagy, characterized by an increase in the formation of Cyto-ID® Autophagy Detection dye-labeled autophagosomes, MDC fluorescent dye-labeled autophagic vacuoles and acridine orange-labeled acidic vesicular organelles (AVOs), was observed in f-PDT-treated cells. TEM also revealed double-membrane autophagosome structures 1 hour after f-PDT. Most importantly, when pretreated with 3-MA, the two cell lines showed more significant photo-cytotoxicity and apoptotic cell death compared to those exposed to f-PDT alone (P < 0.05). CONCLUSION: Chlorophyllin f-mediated PDT exerts anti-tumor activity by inducing apoptosis and autophagy, and most importantly, autophagy inhibition enhances f-PDT-mediated apoptotic cell death. These results suggest that chlorophyllin f is a new, effective photosensitizer and that the combination of f-PDT with autophagy inhibitors may be an attractive therapeutic strategy against human non-muscle invasive bladder cancer.	bladder
Arsenic exposure and bladder cancer: quantitative assessment of studies in human populations to detect risks at low doses.	While exposures to high levels of arsenic in drinking water are associated with excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels (e.g., <100-200 µg/L) generally are not. Lack of significant associations may result from methodological issues (e.g., inadequate statistical power, exposure misclassification), or a different dose-response relationship at low exposures, possibly associated with a toxicological mode of action that requires a sufficient dose for increased tumor formation. The extent to which bladder cancer risk for low-level arsenic exposure can be statistically measured by epidemiological studies was examined using an updated meta-analysis of bladder cancer risk with data from two new publications. The summary relative risk estimate (SRRE) for all nine studies was elevated slightly, but not significantly (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97-1.44, p-H=0.034). The SRRE was statistically significantly lower than relative risks predicted for never smokers in the United States based on linear extrapolation of risks from higher doses in southwest Taiwan to arsenic water exposures >10 µg/L for more than one-third of a lifetime. By contrast, for all study subjects, relative risks predicted for one-half of lifetime exposure to 50 µg/L were just above the upper 95% CI on the SRRE. Thus, results from low-exposure studies, particularly for never smokers, were statistically inconsistent with predicted risk based on high-dose extrapolation. Additional studies that better characterize tobacco use and stratify analyses of arsenic and bladder cancer by smoking status are necessary to further examine risks of arsenic exposure for smokers.	bladder
Follow-up after cystectomy: regularly scheduled, risk adjusted, or symptom guided? Patterns of recurrence, relapse presentation, and survival after cystectomy.	AIMS: To evaluate the efficacy of follow-up based on the patterns of recurrence, relapse presentation and survival after cystectomy, and to define a risk adjusted follow-up schedule. PATIENTS AND METHODS: The records of 343 patients with regular follow-up after cystectomy were reviewed for primary site of recurrence, accompanying symptoms, means of recurrence diagnosis, and clinicopathological factors. Based on Cox proportional hazard models, and the results of imaging studies low and high risk groups are identified and a risk adjusted follow-up protocol is proposed. RESULTS: The risk of a recurrence was related to increasing pT, tumour positive lymph nodes, tumour positive surgical margins, and pre-operative dilatation of the upper urinary tract, and low and high risk groups were defined consequently. 84% of all recurrences occurred within 2 years, with only one recurrence beyond 2 years in the low risk group. Although the minority of all patients (34%) is asymptomatic at time of recurrence, symptomatic recurrences were adversely associated with survival. CT-scans and chest X-rays accounted for 90% of the diagnostic tools to detect a recurrence in patients without symptoms. CONCLUSIONS: Asymptomatic patients may benefit from early treatment after disease recurrence. A risk adjusted follow-up strategy based on stage of disease and additional clinicopathological factors can dichotomise patients at high and low risk for recurrence. The small benefit in survival after early detection has to be confirmed in future studies, and weighed against the available treatment options of recurrences and their subsequent costs.	bladder
Assessment of the radiation-equivalent of chemotherapy contributions in 1-phase radio-chemotherapy treatment of muscle-invasive bladder cancer.	PURPOSE: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. METHODS AND MATERIALS: A standard logistic dose-response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. RESULTS: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval -0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. CONCLUSION: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.	bladder
Genomic characterization of three urinary bladder cancer cell lines: understanding genomic types of urinary bladder cancer.	Several genomic regions are frequently altered and associated with the type, stage and progression of urinary bladder cancer (UBC). We present the characterization of 5637, T24 and HT1376 UBC cell lines by karyotyping, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis. Some cytogenetic anomalies present in UBC were found in the three cell lines, such as chromosome 20 aneuploidy and the loss of 9p21. Some gene loci losses (e.g. CDKN2A) and gains (e.g. HRAS, BCL2L1 and PTPN1) were coincident across all cell lines. Although some significant heterogeneity and complexity were detected between them, their genomic profiles exhibited a similar pattern to UBC. We suggest that 5637 and HT1376 represent the E2F3/RB1 pathway due to amplification of 6p22.3, concomitant with loss of one copy of RB1 and mutation of the remaining copy. The HT1376 presented a 10q deletion involving PTEN region and no alteration of PIK3CA region which, in combination with the inactivation of TP53, bears more invasive and metastatic properties than 5637. The T24 belongs to the alternative pathway of FGFR3/CCND1 by presenting mutated HRAS and over-represented CCND1. These cell lines cover the more frequent subtypes of UBC and are reliable models that can be used, as a group, in preclinical studies.	bladder
Diagnostic accuracy of (11)C-choline PET/CT in preoperative lymph node staging of bladder cancer: a systematic comparison with contrast-enhanced CT and histologic findings.	AIM: The aim of this study was to evaluate the role of C-choline PET/CT in the preoperative evaluation of the nodal involvement of patients with bladder carcinoma (BC) suitable for radical cystectomy and extended pelvic lymph node dissection in comparison with contrast-enhanced CT (CECT) using the pathologic specimen as reference standard. PATIENTS AND METHODS: Twenty-six consecutive patients (69.5 ± 9.3 years; range, 49-84) with histologically proven transitional cell BC were treated with radical cystectomy and pelvic lymph node dissection and were enrolled from April 2011 to January 2013. In all patients, paravesical, internal, eternal, and common iliac nodes as well as obturatory, presacral, preaortic, and precaval lymph nodes (LNs) were dissected up to the origin of the inferior mesentery artery. The areas of the LN dissection were grouped as follow: region A included preaortic and precaval LNs; region B included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the right pelvis; region C included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the left pelvis. C-choline PET/CT and abdominal CECT were used to assess the presence of lymph node metastases on a per patient, region, and lesion analysis using the results of surgical specimens obtained at operation as criterion standard. RESULTS: Seven of 26 patients (26.9%) showed nodal metastases at pathologic analysis. Overall, 844 LNs were evaluated, and 38 of them (4.5%) showed metastatic involvement. On a patient-based analysis, C-choline PET/CT showed a sensitivity of 42% and specificity of 84%, whereas, CECT showed a sensitivity of 14% and specificity of 89%. On a region-based analysis, C-choline PET/CT showed a sensitivity of 11% and specificity of 82%, whereas CECT showed a sensitivity of 5% and specificity of 80%. On a lesion (LN)-based analysis, C-choline PET/CT showed a sensitivity of 10% and specificity of 64%, whereas CECT showed a sensitivity of 2% and specificity of 63%. CONCLUSIONS: C-choline PET/CT could provide additional diagnostic information in preoperative nodal staging of patients with invasive BC in comparison with CECT. A study with a larger population should determine if C-choline PET/CT could be recommended as a routine technique in high-risk patients with BC.	bladder
TGF-β-induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12.	PURPOSE: TGF-β promotes tumor invasion and metastasis by inducing an epithelial-mesenchymal transition (EMT). However, the underlying mechanisms causing this are not entirely clear. Long noncoding RNAs (lncRNA) have been shown to play important regulatory roles in cancer progression. The lncRNA malat1 (metastasis associated lung adenocarcinoma transcript 1) is a critical regulator of the metastasis phenotype of lung cancer cells. EXPERIMENTAL DESIGN: We, therefore, investigated whether TGF-β regulates malat1 expression to promote tumor metastasis of bladder cancer. The expression levels of malat1 and EMT markers were assayed in specimens of bladder cancer. The role of malat1 in regulating bladder cancer metastasis was evaluated in cell and animal models. RESULTS: TGF-β induces malat1 expression and EMT in bladder cancer cells. malat1 overexpression is significantly correlated with poor survival in patients with bladder cancer. malat1 and E-cadherin expression is negatively correlated in vitro and in vivo. malat1 knockdown inhibits TGF-β-induced EMT. malat1 is associated with suppressor of zeste 12 (suz12), and this association results in decrease of E-cadherin expression and increase of N-cadherin and fibronectin expression. Furthermore, targeted inhibition of malat1 or suz12 suppresses the migratory and invasive properties induced by TGF-β. Finally, we demonstrated that malat1 or suz12 knockdown inhibits tumor metastasis in animal models. CONCLUSION: These data suggest that malat1 is an important mediator of TGF-β-induced EMT, and suggest that malat1 inhibition may represent a promising therapeutic option for suppressing bladder cancer progression.	bladder